Chronic Fatigue Study That Sparked Ban May Have Been Flawed

By Elizabeth Lopatto and Michelle Fay Cortez -
May 31, 2011

A 2009 study on chronic fatigue
syndrome that led to a ban on blood donations from sufferers of
the disease may have been spoiled by laboratory mistakes,
according to the science magazine that published the research.

While the study linked the syndrome to the mouse virus
XMRV, at least 10 trials since then haven’t been able to
duplicate the results, the journal Science said in an editorial
published today. New research also indicates the blood samples
used in 2009 likely were contaminated with the virus in the lab,
Science said.

The study’s validity “is now seriously in question,”
Bruce Alberts, editor-in-chief of Science, said in the
editorial.

Science requested a voluntary retraction from the 2009
study’s authors, said spokeswoman Natasha Pinol in a telephone
interview. Judy Mikovits, one of the study’s authors, contacted
the journal on May 30 to inform them she disagreed with the
editorial expression of concern, Pinol said.

“We feel this is an extremely premature action which is
not in the best interest of the scientific community or human
health,” Mikovits said in a letter to Science published on the
website of the Whittemore Peterson Institute for Neuro-Immune
Disease. “We respectfully request that you allow the scientific
process to run its course unhindered by bias.”

A phone call to Mikovits’s office at the Whittemore
Institute in Reno, Nevada, wasn’t returned. The trial was led by
Vincent Lombardi of the institute and Francis Ruscetti, a
National Cancer Institute scientist in Frederick, Maryland.

Extremely Disappointed

“We are extremely disappointed that the editor of Science
has published an ‘editorial expression of concern,’” said
Annette Whittemore, president of the Whittemore Institute, in an
e-mail. “The authors of the Lombardi study believe that it is
premature to conclude that the negative studies are accurate or
change the conclusions of the original studies and we fully
agree.”

The study led the American Red Cross, the largest U.S.
supplier of blood products, to announce in December 2010 that it
would no longer allow donors with chronic fatigue syndrome. The
U.S. National Institutes of Health is sponsoring studies to
determine if a link between XMRV and chronic fatigue syndrome
can be confirmed.

Clinical Trial

The study of 150 patients with chronic fatigue syndrome and
another 150 healthy volunteers should be complete by early 2012,
said Ian Lipkin, a professor of epidemiology at Columbia
University in New York, who is leading the effort. Until the
research is complete, it’s too soon to know whether there is a
link between a virus and chronic fatigue, he said.

“Calls to retract the paper at this point are premature,”
said Lipkin, director of Columbia’s Center for Infection and
Immunity, in a telephone interview. “We need to let this study
take its course, look at the data in a coherent fashion and
figure out what it tells us.” While interesting, “the
publications don’t dissuade us from continuing our work.”

More than 1 million people in the U.S. have chronic fatigue
syndrome, more than those with multiple sclerosis, lupus, or
lung cancer, according to the Centers for Disease Control and
Prevention in Atlanta. The condition, which saps people of
energy for months or years, has no proven cause and mostly
affects women ages 30 to 50, according to the National
Institutes of Health. Women are four times more likely than men
to develop the disease.

Original Conclusion

The study, published in October 2009, found XMRV in the
blood of two-thirds of tissue samples taken from people with the
condition and 3.7 percent of a group of healthy individuals.

Scientists led by Jay Levy, a professor of medicine at the
University of California, San Francisco, said in a study today
that the link was probably because chemicals and cell lines used
in the lab where it was detected were contaminated with XMRV.

Levy’s group examined 61 patients with chronic fatigue
syndrome, 43 of whom had been previously reported as infected
with XMRV. Using a similar procedure to the original paper, the
scientists tested the blood. They didn’t find any evidence of
XMRV or any other mouse-related virus.

In addition, the Levy study demonstrated that human serum
quickly kills the virus, making an infection unlikely.

‘Totally Surprised’

“When that paper came out I was totally surprised and
suspicious,” Levy said today in a telephone interview. “Who
knew there would be pressure on the government to do these
expensive studies? I’ve never been around anything quite so
dramatic and misleading and misunderstood for so long. There are
financial ramifications, and medical and health ramifications.”

The Whittemore researchers didn’t claim the virus caused
chronic fatigue syndrome. People with the condition may be more
vulnerable to the virus or it may be a so-called passenger
virus, one that shows up in diseased tissue without being a
cause of the illness, the researchers said.

A second paper also published today by Science showed that
XMRV was created by recombining two mouse leukemia viruses while
scientists passed a human prostate tumor to mice. The cell line
derived from that graft is the best explanation for the
detection of XMRV in human samples.

“Taken together, these results close the door on XMRV as a
cause of human disease,” John Coffin, a professor at Tufts
University School of Medicine in Boston and a co-author of the
paper, said in a statement.